PROJECT SUMMARY Chronic low back pain is a significant socioeconomic burden in the United States, one that consumes approximately $100 billion through lost wages and decreased productivity. In the absence of gross structural abnormalities or radicular pain, the specific source of low back pain is difficult to identify with currently available clinical techniques like physical examination, radiography and magnetic resonance imaging (MRI), leading to the oft-issued diagnosis of ?non-specific? back pain. Thus, there is a pressing need to improve upon the sensitivity of clinical tools for diagnosing back pain. The lumbar intervertebral discs naturally degenerate with age and are implicated as a causative factor in low back pain. The specific functional consequences of disc degeneration and their relationship to low back pain are not well defined, however. Furthermore, while there has been extensive research on cadaveric human discs to show that age-related degeneration affects spine biomechanics ex vivo, there has been little effort to track the in vivo function of the lumbar spine. Our global hypothesis for this work is that the in vivo function of the lumbar spine is affected by age-related alterations in disc composition. Our lab has developed a method to dynamically track elements of the musculoskeletal system in vivo by registering volumetric models from MRI to biplanar radiographic images. In these experiments, we will examine how age affects spine function during a simulated clinical exam (forward flexion), and as a result of activities of daily living (ADL). In Specific Aim 1, we will recruit asymptomatic human participants into four age groups, develop three-dimensional models of their lumbar spines from MRI data, and then map those models to live radiographic data of their spine during forward flexion, a motion used in standard clinical exams to assess back pain. We will evaluate changes in vertebral position and intervertebral disc strain with age. In Specific Aim 2, using the same asymptomatic age groups, we will generate three-dimensional models of the lumbar discs in the morning and then again in the evening, taking advantage of the natural fluctuations in disc strain due to ADL. We will evaluate changes in disc strain over the course of the day and how these changes are affected by age. In both Aims, we will correlate mechanical parameters to MRI and serum/urine biomarkers of disc composition. Ultimately, we aim to validate biomechanical benchmarks and biomarkers that can discriminate between patients with altered spine function due purely to natural aging and those that have altered function due to disease. In these studies, we will develop critical information on age-related alterations in lumbar spine kinematics and disc function. These experiments are a critical foundation for future work in defining the relationships between spine function and spine pathology.